Immunotherapy: the beacon of hope for cancer treatment

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Cancer is an illness that has touched practically everybody’s lives in some way. The disease is indiscriminate, affecting friends, relatives, teachers and colleagues. Although mostly associated with more elderly patients, cancers such as melanoma and leukaemia exist in any age group.

‘Cancer’ is a very broad term for a number of different conditions. It is used for a disease of any organ, identified by an uncontrolled growth of tissue. The steps that precede the development of cancer can vary in type and order, with the resulting mass of tissue being the recognisable element. In the multitude of steps leading up to cancer, there is an incredible number of things that have to go wrong. Our cells have several controls in place to stop unregulated replication and growth from happening, all of which are overcome in cancerous tissue.

Usually, various immune cell types are key for the healing of tissue or removal of unhealthy cells. In cancer, despite the unusual cells, the immune system does not react. Until relatively recently, it was thought that the immune cells just couldn’t ‘see’ cancer. It took a group of scientists led by Jim Allison at the University of California, Berkeley to realise that the immune system wasn’t ignoring cancer, it was being tricked into thinking it was safe.

To recognise healthy vs. unhealthy cells, ‘T cells’ (a very important immune cell type) will form an ‘immune synapse’ with the cell of interest. The best analogy for this is the door of a nightclub. The T cell acts as a bouncer, the cell a reveller that wants to get in. If the clubgoer presents their I.D. and behaves soberly enough, they are allowed to pass by. If they are too drunk or do not have I.D., they are turned away (here, the cell is destroyed, rather than being put into a taxi home). Imagine a cancer cell as a 17-year-old that has had far too much to drink. They want to get in but shouldn’t. Using more sober friends around them and a fake I.D., they are able to sneak past the bouncer. Equivalently, the cancer cell can use healthy cells around it and a ‘fake I.D.’ in the form of a molecule that is present on healthy cells. It fools the T cells and is allowed to continue growing and dividing out of control.

Once it was realised that the immune system was being tricked, scientists started to work out why it happened and how to stop it. The most successful approach has been a group of drugs known as ‘check-point inhibitors’. In one example, a molecule called PD-1 is blocked, which, sticking with the club analogy, would be like blocking the presentation of the fake I.D. It stops the immune system from being confused, allowing it to see the cancer cells as dangerous and destroy them.

Anti-PD-1 (the PD-1-blocker) drugs are the most famous and successful therapy that harnesses the immune system against cancer. This ‘immunotherapy’ has become a shining beacon of light for cancer treatment. The anti-PD-1 drug pembrolizumab (sold as Keytruda) has been approved for a number of different types of cancer. More and more other check-points are being researched as well, with the successes becoming less unusual.

Check-point inhibitors, however, are not the only form of immunotherapy that is being developed to treat cancer. In the same way that vaccines can train the immune system to attack viruses, scientists are developing methods to sample individual cancer tissues and induce immune system recognition of the diseased tissue. There are other techniques that introduce T cells from outside the cancer patient, whether from a donor or cells that have been removed from the patient, trained to attack cancer, and then reintroduced.

There are now reportedly 940 ‘new’ cancer immunotherapeutic drugs being tested in the clinic. These reflect more than 500,000 cancer patients in more than 3,000 clinical trials. These are incredible numbers, and yet still pale in comparison to the number of trials that are testing immunotherapy combinations or pairings of immunotherapies with chemotherapy or radiation.

Unfortunately, immunotherapies are not without their side effects. Traditional cancer therapies are infamous for the associated illnesses, with surgery, radiotherapy and chemotherapy all coming with degrees of pain and sickness. The developing immunotherapies may not have the same ailments as the so-called ‘cut, burn and poison’ techniques, but they are still present. A notable example is liver disease caused by check-point-inhibitors, as cancer patients develop liver cirrhosis and eventually suffer from liver failure. Although scientists are working on it, we are still trying to figure out exactly how these side effects happen and how to stop them.

In a disease as aggressive as cancer, false hope is a cruel card to play. Due to the enormous number of lives that are affected, it isn’t difficult for cancer to make headlines. Whether something new has been found to cause cancer, or a new therapy is developed, the news will be screamed from outlets everywhere. There are also the conspiracy theories – those whispers that say that a ‘cure’ for cancer has been found, it is just too expensive to use.

The truth is that cancer is far too broad a term for there to be a ‘cure’. There is no one single disease that is ‘cancer’ to treat. Instead, better therapies can be developed that improve prognosis, get rid of the cancerous tissue quicker and boost the chances of survival. The cancer could come back, or a different type could develop. As doom and gloom as this sounds, it is the truth. Immunotherapy, however, is a pretty good hope. It is crossing the barriers between cancer types and can be used for multiple versions of the out of control tissues. The side effects are being worked out and the survival rates are far greater than chemotherapy alone. It is not ready to single-handedly fight cancer yet, but it’s setting us on a better track.